Present and Future of Parkinson's Disease in Spain: PARKINSON-2030 Delphi Project

This project was funded by Zambon S.A.U.D.S.G., M.B.-E., J.K., F.P.-E., F.V., M.-R.L. and J.P. declare no conflict of interest. M.C. has received honoraria for lecturing or advisory boards from AbbVie, Bial and Zambon. F.E.-S. has received honoraria as a speaker, support to attend scientific meetings and grants for conducting studies from Abbvie, Bial, Boston Scientifice, Medtronic, Merz Pharma, Teva, UCB Pharma and Zambon. E.F. has received advisory, consulting and lectures fees from Abbvie, Teva, Bial, Zambon and Neuraxpharm. For P.J.G.R., no specific funding was received for this study. The author reports no conflicts of interest. In the previous 12 months, this author received research support from Aller gan and UCB, personal compensation as a consultant/scientific advisory boards from Italfarmaco, Britannia, Bial and Zambon and speaking honoraria from Italfarmaco, Zambon, Allergan and Abbvie. F.G. received grants from the Instituto de Salud Carlos III and from the European Commission (Horizon 2020). He received consulting honoraria from Exeltis and for lecturing from Zambon and TEVA. L.L.-M. has received compensated advisory services, consulting, research grant support, or speaker honoraria from AbbVie, Acorda, Bial, Intec Pharma, Italfarmaco, Pfizer, Roche, Teva, UCB and Zambon. J.C.M.C. has received honoraria as a speaker from Abbvie, Allergan, Bial, Boehringer Ingelheim, GSK, Krka Farmaceutica, Merz Pharma, Ipsen, Italfarmaco, Lundbeck, Medtronic, TEVA, UCB and Zambon; research grants from Abbvie, Allergan, Merz Pharma, Italfarmaco, Lundbeck, UCB and Zambon; and participated in the advisory boards of Abbvie, Allergan, GSK, Bial, Merz Pharma, Merck, Boehringer Ingelheim, Ipsen, Italfarmaco, Lundbeck, Orion, UCB and Zambon. P.M. has received support for attending meetings and/or honorarium for lecturing from Abbott, Allergan, Abbvie, Bial, Britannia, Italfarmaco, Merz, UCB, Roche, Teva and Zambon. J.M.S. has participated in advisory boards and pharmaceutical industry-sponsored symposia for Zambon, UCB, Bial, Italfarmaco, Eisai España and Abbvie Spain. B.T.: speaking fees, AbbVie, and travel expenses, Italfarmaco. R.Y. has received honoraria as a speaker for Bial, Italfarmaco, Teva and Zambon, support to attend scientific meetings from Alter, for consultancy from Bial, and sponsored for conducting studies from Zambon and Lundbeck. A.A. is employed and receives personal fees from Zambon.Parkinson's disease (PD) is a chronic progressive and irreversible disease and the second most common neurodegenerative disease worldwide. In Spain, it affects around 120.000-150.000 individuals, and its prevalence is estimated to increase in the future. PD has a great impact on patients' and caregivers' lives and also entails a substantial socioeconomic burden. The aim of the present study was to examine the current situation and the 10-year PD forecast for Spain in order to optimize and design future management strategies. This study was performed using the modified Delphi method to try to obtain a consensus among a panel of movement disorders experts. According to the panel, future PD management will improve diagnostic capacity and follow-up, it will include multidisciplinary teams, and innovative treatments will be developed. The expansion of new technologies and studies on biomarkers will have an impact on future PD management, leading to more accurate diagnoses, prognoses, and individualized therapies. However, the socio-economic impact of the disease will continue to be significant by 2030, especially for patients in advanced stages. This study highlighted the unmet needs in diagnosis and treatment and how crucial it is to establish recommendations for future diagnostic and therapeutic management of PD.PfizerRocheTeva Pharmaceutical IndustriesUCBEuropean CommissionInstituto de Salud Carlos IIIHorizon 202

Endosymbiont communities in Bemisia tabaci: a metagenomic approach

Este trabajo es parte de un programa de investigación que tiene como objetivo dilucidar la evolución de las bacterias endosimbiontes utilizando los consorcios insecto-bacteria como modelo. Los diferentes estudios realizados sobre los insectos y sus bacterias endosimbiontes han arrojado luz sobre los cambios ocurridos tras la adquisición de una forma de vida intracelular, así cómo la interacción entre diferentes endosimbiontes formando comunidades endosimbioticas. Dos son los objetivos principales de este trabajo. El primera (capítulos “Portiera y su socio Hamiltonella” y “El tercer pasajero: Cardinium cBtQ1)” trata de analizar y describir las relaciones de la comunidad endosimbiótica en B. tabaci utilizando una cepa de laboratorio como modelo. El segundo (capítulo “Evolución genómica del género Portiera”) describe la evolución el endosimbionte primario Portiera en las moscas blancas y su uso para la datación molecular. El capítulo "Portiera y su socio Hamiltonella" describe los patrones de distribución y la ultraestructura de los diferentes endosimbiontes albergados por B. tabaci BT-QVLC. La secuenciación, anotación y análisis de los genomas de Portiera y Hamiltonella revelan su papel como proveedores de aminoácidos esenciales y vitaminas / cofactores a su anfitrión. El capítulo "El tercer pasajero: Cardinium cBtQ1" se centra en los cambios genómicos que resultan de la aclimatación de este endosimbionte a su hospedador B. tabaci, así como las posibles interacciones con su anfitrión y los otros endosimbiontes presentes. Un análisis genómico comparativo de varios Bacteroidetes muestra la evolución del repertorio de génico en la familia Amoebophilaceae. Finalmente, se discuten los genes de “deslizamiento” que se encuentran Cardinium cBtQ1 y su posible participación en la movilidad del endosimbionte. El capítulo “Evolución genómica del género Portiera” analiza tres genomas adicionales de Portiera de diferentes especies de moscas blancas. Los estudions de genómica comparativa han permitido la reconstrucción del Último Ancestro Común para las diversas cepas de Portiera existentes, las sus capacidades metabólicas, así como para describir sus tasas de sustitución nucleotídicas. Por último, los genes Portiera se han utilizado para estimar el tiempo de divergencia de diferentes moscas blancas.Whiteflies are important agricultural insect pests, whose evolutionary success is related to a long-term association with a bacterial endosymbiont, Candidatus Portiera aleyrodidarum. To completely characterize this endosymbiont clade, we sequenced the genomes of three new Portiera strains covering the two extant whitefly subfamilies. Using endosymbiont and mitochondrial sequences we estimated the divergence dates in the clade and used these values to understand the molecular evolution of the endosymbiont coding sequences. Portiera genomes were maintained almost completely stable in gene order and gene content during more than 125 million years of evolution, except in the Bemisia tabaci lineage. The ancestor had already lost the genetic information transfer autonomy but was able to participate in the synthesis of all essential amino acids and carotenoids. The time of divergence of the B. tabaci complex was much more recent than previous estimations. The recent divergence of biotypes B (MEAM1 species) and Q (MED species) suggests that they still could be considered strains of the same species. We have estimated the rates of evolution of Portiera genes, synonymous and nonsynonymous, and have detected significant differences among-lineages, with most Portiera lineages evolving very slowly. Although the nonsynonymous rates were much smaller than the synonymous, the genomic dN/dS ratios were similar, discarding selection as the driver of among-lineage variation. We suggest variation in mutation rate and generation time as the responsible factors. In conclusion, the persistence of the long-term association of Portier

Elastic, dielectric and electromechanical properties of (Bi0.5Na0.5)TiO3-BaTiO3 piezoceramics at the morphotropic phase boundary region

A systematic study of the functional properties of the (1-x)(Bi0.5Na0.5)TiO3–xBaTiO3 (BNT-xBT) piezoceramic system for 0.05 = x = 0.07 is performed. The samples are obtained through the conventional solid-state route. The expected microstructure for these compounds, with no significant dependence on the composition, is verified by field-emission scanning electron microscopy. The morphotropic phase boundary (MPB) is detected for x = 0.06–0.07 by means of the Rietveld analysis of X-ray diffraction data. The dielectric spectra show a frequency-independent, completely diffuse phase transition with a composition-dependent diffusivity coefficient. The depolarization temperature is effectively evaluated from pyroelectric measurements, the value being strongly dependent on the composition. A significant contribution of the extrinsic effect to elastic, dielectric and electromechanical properties is revealed for MPB BNT-xBT. The Bi3+ substitution by Ba2+ leads to the formation of A-site vacancies, which give rise to the enhancement of domain wall motion, as occurs in other perovskite-type piezoelectrics. Good functional properties are achieved for x = 0.07 (d33 = 180 pC/N), which are similar or even better than those obtained by complex synthesis routes. This system exhibits a remarkable stability in the permittivity that has hitherto not been reported. This fact may open the way for BNT-BT compositions to be used in specific applications in which lead-free piezoceramics have previously been employed with little success, e.g. in high power devices.Postprint (author's final draft

A High-Efficiency Isolated Wide Voltage Range DC-DC Converter Using WBG Devices

The recent release of the standard USB-PD 3.1 speci es variable output voltages from 5 V to 48 V featuring a step forward towards a universal adaptor but rising new challenges for the converter topologies used up to now. In such applications, a rst AC-DC stage is followed by a DC-DC stage. In this paper, emerging WBG technologies are applied to the asymmetrical half-bridge yback topology, demonstrating the potential of such combination as a wide voltage range DC-DC stage. Its suitability for high-density and high-ef ciency USB-PD Extended Power Range (EPR) and battery charger applications is discussed. The impact of different switching technologies, silicon and wide band gap, is analyzed. A general method to dimension the converter is presented and an iterative process is used to evaluate the theoretical ef ciency under different conditions and switching devices. Finally, the advantages of the presented converter using Gallium Nitride (GaN) devices are demonstrated in a 240 W DC-DC prototype. It achieves a full load ef ciency of 98%, and it is able to deliver an output voltage from 5 V to 48 V with input voltage range from 120 V to 420 V, as well an outstanding power density of 112 W/inch3 uncased.Infineon Technologies AG through the Spanish Regional Project P20_00265 BRNM-680-UGR20Spanish Ministry of Science MCIN/AEI PID2020-117344RB-I0

Complete Assembly of the Genome of an Acidovorax citrulli Strain Reveals a Naturally Occurring Plasmid in This Species

Acidovorax citrulli is the causal agent of bacterial fruit blotch (BFB), a serious threat to cucurbit crop production worldwide. Based on genetic and phenotypic properties, A. citrulli strains are divided into two major groups: group I strains have been generally isolated from melon and other non-watermelon cucurbits, while group II strains are closely associated with watermelon. In a previous study, we reported the genome of the group I model strain, M6. At that time, the M6 genome was sequenced by MiSeq Illumina technology, with reads assembled into 139 contigs. Here, we report the assembly of the M6 genome following sequencing with PacBio technology. This approach not only allowed full assembly of the M6 genome, but it also revealed the occurrence of a ∼53 kb plasmid. The M6 plasmid, named pACM6, was further confirmed by plasmid extraction, Southern-blot analysis of restricted fragments and obtention of M6-derivative cured strains. pACM6 occurs at low copy numbers (average of ∼4.1 ± 1.3 chromosome equivalents) in A. citrulli M6 and contains 63 open reading frames (ORFs), most of which (55.6%) encoding hypothetical proteins. The plasmid contains several genes encoding type IV secretion components, and typical plasmid-borne genes involved in plasmid maintenance, replication and transfer. The plasmid also carries an operon encoding homologs of a Fic-VbhA toxin-antitoxin (TA) module. Transcriptome data from A. citrulli M6 revealed that, under the tested conditions, the genes encoding the components of this TA system are among the highest expressed genes in pACM6. Whether this TA module plays a role in pACM6 maintenance is still to be determined. Leaf infiltration and seed transmission assays revealed that, under tested conditions, the loss of pACM6 did not affect the virulence of A. citrulli M6. We also show that pACM6 or similar plasmids are present in several group I strains, but absent in all tested group II strains of A. citrulli

Non-Intrusive Tank-Filling Sensor Based on Sound Resonance

Different types of fill-level measurement systems exist in the market, but most of them imply some type of intrusion in the tank itself. In this paper, a reconfigurable system based on sound resonance for measuring the fill-level of a tank from the exterior is presented. A relation between sound resonance frequencies and the content of the tank has been found, especially as the tank gets closer to being full. A prototype has been created using reconfigurable technologies combined with wireless communications in order to control the system from an ad hoc application. With this prototype, the fill-level of different tanks has been measured with good resolution, especially when the tank is over half of its capacity

Predictors of Loss of Functional Independence in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up and Comparison with a Control Group

Background and objective: The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson’s disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD). Patients and Methods: PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%. Results: In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen’s effect size = −0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2. Conclusions: In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term

A framework for the analysis and optimization of encoding latency for multiview video

We present a novel framework for the analysis and optimization of encoding latency for multiview video. Firstly, we characterize the elements that have an influence in the encoding latency performance: (i) the multiview prediction structure and (ii) the hardware encoder model. Then, we provide algorithms to find the encoding latency of any arbitrary multiview prediction structure. The proposed framework relies on the directed acyclic graph encoder latency (DAGEL) model, which provides an abstraction of the processing capacity of the encoder by considering an unbounded number of processors. Using graph theoretic algorithms, the DAGEL model allows us to compute the encoding latency of a given prediction structure, and determine the contribution of the prediction dependencies to it. As an example of DAGEL application, we propose an algorithm to reduce the encoding latency of a given multiview prediction structure up to a target value. In our approach, a minimum number of frame dependencies are pruned, until the latency target value is achieved, thus minimizing the degradation of the rate-distortion performance due to the removal of the prediction dependencies. Finally, we analyze the latency performance of the DAGEL derived prediction structures in multiview encoders with limited processing capacity

When Spinal Neuromodulation Meets Sensorimotor Rehabilitation: Lessons Learned From Animal Models to Regain Manual Dexterity After a Spinal Cord Injury

Electrical neuromodulation has strongly hit the foundations of spinal cord injury and repair. Clinical and experimental studies have demonstrated the ability to neuromodulate and engage spinal cord circuits to recover volitional motor functions lost after the injury. Although the science and technology behind electrical neuromodulation has attracted much of the attention, it cannot be obviated that electrical stimulation must be applied concomitantly to sensorimotor rehabilitation, and one would be very difficult to understand without the other, as both need to be finely tuned to efficiently execute movements. The present review explores the difficulties faced by experimental and clinical neuroscientists when attempting to neuromodulate and rehabilitate manual dexterity in spinal cord injured subjects. From a translational point of view, we will describe the major rehabilitation interventions employed in animal research to promote recovery of forelimb motor function. On the other hand, we will outline some of the state-of-the-art findings when applying electrical neuromodulation to the spinal cord in animal models and human patients, highlighting how evidences from lumbar stimulation are paving the path to cervical neuromodulation

Longitudinal analysis of the Non-Motor Symptoms Scale in Parkinson's Disease (NMSS): An exploratory network analysis approach

Introduction Parkinson's disease (PD) is a multisystem neurodegenerative disorder characterized by motor and non-motor symptoms. In particular, non-motor symptoms have become increasingly relevant to disease progression. This study aimed to reveal which non-motor symptoms have the highest impact on the complex interacting system of various non-motor symptoms and to determine the progression of these interactions over time. Methods We performed exploratory network analyses of 499 patients with PD from the Cohort of Patients with Parkinson's Disease in Spain study, who had Non-Motor Symptoms Scale in Parkinson's Disease ratings obtained at baseline and a 2-year follow-up. Patients were aged between 30 and 75 years and had no dementia. The strength centrality measures were determined using the extended Bayesian information criterion and the least absolute shrinkage and selection operator. A network comparison test was conducted for the longitudinal analyses. Results Our study revealed that the depressive symptoms anhedonia and feeling sad had the strongest impact on the overall pattern of non-motor symptoms in PD. Although several non-motor symptoms increase in intensity over time, their complex interacting networks remain stable. Conclusion Our results suggest that anhedonia and feeling sad are influential non-motor symptoms in the network and, thus, are promising targets for interventions as they are closely linked to other non-motor symptoms